Wiesbaden, Germany – Last night Bavarian Nordic dropped the unfortunate news that the phase 3 PROSPECT trial exploring the PROSTVAC vaccine in combination with GM-CSF in asymptomatic or minimally symptomatic metastatic castrate resistant prostate cancer (CRPC) was futile.
Source: Bavarian Nordic
Once you miss the overall survival (OS) endpoint, that’s it folks – there’s no other choice but to say the therapy failed, harsh though that may sound.
There are, however, a number of important points to consider from here that are worthy of further discussion.
Here, we post an analytical review and look at a number of factors that could have impacted the outcome. It’s rarely one simple thing because the immune system is highly complex and multi-faceted.
Hopefully there will be important learnings from this study that will advance the IO and prostate cancer fields.
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William Coley first used live bacteria as an immune stimulant to treat cancer way back in 1893. Since then, however, progress with innate immunotherapy has been surprisingly very slow.
Queen Mary Rose Garden, Regents Park, Summer 2015
Indeed, to date only one therapeutic cancer vaccine has actually been approved by the FDA (Sipuleucel-T, Provenge, Dendreon), one oncolytic virus was approved in China back in 2006 (H101, a direct derivative of the E1B55k-deleted Onyx-015 that had modest activity at best) and another could soon be approved by the FDA later this year (T-VEC, Amgen).
In today’s review, we take a look at the oncolytic viral space and explore the issues, challenges and companies involved. Is this all set to be a bed of roses, or is a thorny future predicted?
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With the launch of Episode 4 of the Novel Targets podcast today, I wanted to provide some more detailed background and a roadmap for this part of the journey for subscribers. There’s tremendous wealth of data now building up in several areas related to cancer immunotherapy and both interviewees, Drs Oliver Sartor (Tulane) and James Gulley (NCI), touched on many of them.
Thanks to Tom Gajewski’s exciting work, we can broadly think about different tumour types as inflamed (immunogenic) versus non-inflamed (non-immunogenic), which is a helpful starting point. Not all tumours thought to be responsive to immunotherapy will actually respond though, so we still have much work to do on the 70–80% of patients with solid tumours that don’t respond to these therapies.
Anyone who is interested can listen to the latest Novel Targets podcast.
The latest episode explores non-immunogenic tumours, using prostate cancer as an example. In the last third of the show, we do indeed talk about a promising new target that may have relevance not just to prostate cancer, but other tumour types too.
Listen to Episode 4 (open access thanks to our sponsors, Genentech)
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We have been following the results of the checkpoint inhibitors for several years now, first with ipilimumab (Yervoy) and lately with anti-PD1 and PD-L1 inhibitors such as nivolumab, pembrolizumab and MPDL3280A. Irrespective of the antibody used, the best results we’ve seen have in melanoma, lung and bladder, but some tumour types such as colon and prostate cancers have barely been responsive at all.
Why is that?
Can we find ways to make non-responsive solid tumours responsive to immune therapies, and if so, what strategies could we employ to enable improved responses and outcomes?
At the ASCO Genitourinary (GU) meeting in Orlando this weekend there were some interesting hints of what might be possible in the not too distant future.
To learn more about this phenomenon, we conducted an interview with a leading cancer immunologist to find out what they are doing to make a difference in the GU space.
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